Multi-Scale Spatio-Temporal Transformer-Based Imbalanced Longitudinal Learning for Glaucoma Forecasting From Irregular Time Series Images

Glaucoma is one of the major eye diseases that leads to progressive optic nerve fiber damage and irreversible blindness, afflicting millions of individuals. Glaucoma forecast is a good solution to early screening and intervention of potential patients, which is helpful to prevent further deterioration of the disease. It leverages a series of historical fundus images of an eye and forecasts the likelihood of glaucoma occurrence in the future. However, the irregular sampling nature and the imbalanced class distribution are two challenges in the development of disease forecasting approaches. To this end, we introduce the Multi-scale Spatio-temporal Transformer Network (MST-former) based on the transformer architecture tailored for sequential image inputs, which can effectively learn representative semantic information from sequential images on both temporal and spatial dimensions. Specifically, we employ a multi-scale structure to extract features at various resolutions, which can largely exploit rich spatial information encoded in each image. Besides, we design a time distance matrix to scale time attention in a non-linear manner, which could effectively deal with the irregularly sampled data. Furthermore, we introduce a temperature-controlled Balanced Softmax Cross-entropy loss to address the class imbalance issue. Extensive experiments on the Sequential fundus Images for Glaucoma Forecast (SIGF) dataset demonstrate the superiority of the proposed MST-former method, achieving an AUC of 96.6% for glaucoma forecasting. Besides, our method shows excellent generalization capability on the Alzheimer's Disease Neuroimaging Initiative (ADNI) MRI dataset, with an accuracy of 88.2% for mild cognitive impairment and Alzheimer's disease prediction, outperforming the compared method by a large margin. A series of ablation studies further verify the contribution of our proposed components in addressing the irregular sampled and class imbalanced problems.